Clinicians face two major challenges in managing patients with chronic hepatitis C. First, the natural history of chronic hepatitis C remains poorly understood so that predicting the course for an individual patient for whom we are caring remains imprecise. Epidemiologic studies have implicated a number of host factors, such as gender, alcohol consumption, and HIV co-infection, as being associated with rapidly progressive disease. However, the mechanisms by which these interact to alter disease pathogenesis remain unknown. The second challenge is trying to optimize therapy for a diverse population of patients infected with hepatitis C. Although newer therapies for HCV are increasingly effective, there is a large body of evidence to suggest that certain patient populations respond less well to antiviral therapy than others. To date, there have been no prospective studies addressing these issues or the mechanisms by which this may occur. The UNC Liver Diseases Program, under my direction, is currently active in pursuing various studies that focus on these two important themes in hepatitis C. These studies provide the backbone of my mentoring program for junior faculty and fellows who are actively involved in their design, execution, and analysis. For the purposes of this application, I will focus on one ongoing study involving special populations, funded by NIDDK, that investigates antiviral response and resistance in African Americans with chronic hepatitis C (UO1-DK60327- 01, VIRAHEP-C). I will also provide a synopsis of other ongoing studies that form the core of our HCV research program. My immediate career goal is to maintain the trajectory of patient-oriented research at UNC. In the long-term, I would like to direct a multi-disciplinary team of clinical investigators and basic scientists who can work together closely on translational studies of the pathogenesis of chronic viral hepatitis. Finally, my experiences working within the General Clinical Research Center (GCRC) have been very favorable and I would like to become more actively involved in that program. The K-24 award will allow me to attain my goals by relieving me of some of my clinical commitments, thus allowing me to concentrate further on patient-oriented research. It will provide me with additional time to mentor junior faculty and fellows and continue to foster their development within the context of a burgeoning patient-oriented research program.